Prostate cancer


Russ Ingram didn't sense pending calamity when he reported for a company physical seven years ago. After all, he was in good shape and, at 39, still very much a robust young man with no signs of health problems.

During part of the exam, however, the doctor noticed that Ingram's prostate was enlarged. While this can indicate a tumor, often it signals a common benign prostate condition, usually in men much older than Ingram. But a visit to a urologist produced the grim news that his condition was not benign. He had prostate cancer.

"I was devastated," says Ingram. "Due to my age, I didn't think there was anything to worry about. It caught me totally off guard. I 'didn't even know where the prostate was." To be sure, Ingram's case is not typical. His age at diagnosis placed him well outside the primary risk group for prostate cancer.

No One Answer For Testing Or Treatment
Statistically, 80 percent of prostate cancers occur in men over 65. In fact, men in their 30s are not usually tested for prostate cancer in a physical and Ingram says it was just "a fluke" that the doctor discovered the enlarged prostate.

While the disease can strike any man, younger men at increased risk include African Americans, who have double the risk and death rate of white men and often are stricken before age 50. Men with a family link to prostate cancer through brothers or fathers also are at a greater risk of getting the disease before 50.

The American Cancer Society estimates that about 184,500 American men will be diagnosed with prostate cancer this year and 39,200 will die. It is now the second leading cause of cancer death in men, next to lung cancer. Despite the bleak numbers, 89 percent of men diagnosed with the disease will survive at least five years and 63 percent will survive at least 10 years, the society says. These rates are partly due to improved screening tests and diagnostics the Food and Drug Administration has approved that discover cancer in early stages. Also, prostate cancer is very slow growing in some men, who may die of some other cause before the disease takes its toll.

Leading Cancers in Men (1998 estimates)

Detecting Prostate Cancer
The prostate is a male sex gland, about the size of a walnut. It produces a thick fluid that helps propel sperm through the urethra and out of the penis during sex. Because the prostate is just below the bladder and directly in front of the rectum, a doctor can check the size and condition of the gland by inserting a rubber-gloved finger into the rectum. This digital rectal exam (DRE) has for years been the gold standard for detecting prostate cancer as well as the noncancerous disorder benign prostatic hyperplasia (BPH).

In 1985, FDA approved the first test for monitoring blood levels of a substance called prostate specific antigen (PSA), which, when elevated, can indicate cancer presence. Several companies now have approved PSA tests, which, experts say, have revolutionized the screening and monitoring of patients.

PSA is an ideal marker for prostate cancer because it is basically restricted to prostate cells. A healthy prostate will produce a stable amount--typically below 4 nanograms per milliliter, or a PSA reading of "4" or less--whereas cancer cells produce escalating amounts that correspond with the severity of the cancer. A level between 4 and 10 may raise a doctor's suspicion that a patient has prostate cancer, while amounts above 50 may show that the tumor has spread elsewhere in the body.

Most PSA tests measure "total PSA," or the amount that is bound to blood proteins. In March, FDA approved the Tandem R test, which measures not only total PSA but another component called "free PSA," which floats unbound in the blood. Comparing the two helps doctors rule out cancer in men whose PSA is mildly elevated from other causes. A 1995 study in the Journal of the American Medical Association showed that the free PSA test can reduce unnecessary prostate biopsies by 20 percent in patients with a PSA between 4 and 10.

The availability of increasingly sensitive testing devices has created a debate over when men should be tested for prostate cancer, how often, and whether men under 50 with no symptoms should be routinely screened. Opponents say mass screening would be expensive, and the verdict is still out on whether early detection can curb the disease's mortality rate. But proponents say early detection is the closest thing currently to a cure and that it can save lives. The American Cancer Society and the American Urological Association recommend annual PSA tests--along with the digital exam--for all men over 50 and for high-risk men over 40.

The PSA test, though a powerful tool, "is not perfect," says Jean Fourcroy, M.D., urologist and medical officer in FDA's Center for Devices and Radiological Health. Besides being thrown off by noncancerous conditions, the tests can vary between manufacturers. "Patients and physicians should use the same brand of PSA test throughout monitoring because of these possible variations," Fourcroy says.

When PSA or digital tests indicate a strong likelihood that cancer is present, doctors usually order a transrectal ultrasound (TRUS), a probe inserted into the rectum that uses sound waves to "map" the prostate and show any suspicious areas. Doctors then may take biopsies of various sectors of the prostate using tiny hollow needles inserted through the rectum. Biopsies are the only definitive way to determine if prostate cancer is present.

If the biopsy indicates cancer, the doctor then "stages" the tumor based on which biopsy specimens contain cancer, the extent of cancer, and the location of cancer in the specimens (see diagram). Staging also depends on the extent and location of cancer outside the confines of the prostate.

Another important measure, the Gleason score, gauges the probable aggressiveness of the tumor based on the cellular differences of the cancer. Tumor cells that look similar to normal cells tend to be less aggressive, while those distributed randomly with uneven edges are likely to spread rapidly. Two numbers, each from 1 to 5, are assigned. The higher the numbers when the two are added, the more aggressive the tumor is likely to be.

Doctors also examine the ploidy, or number of sets of chromosomes in a cancer cell. Diploid cells, for example, have a complete set of normally paired chromosomes and tend to grow slowly and respond well to therapy.

Recently, some doctors have begun using Partin Tables, a scoring method developed at Johns Hopkins University that uses PSA, Gleason number, and: staging to predict if the disease is confined or has spread to other sites. Doctors also can determine cancer spread with imaging techniques such as bone scans and computerized tomography (CT) scans.

Treating the Disease
Armed with diagnostic data, patients and their doctors must then decide on a treatment course. It is at this point that patients must be well educated, says FDA's Fourcroy. "The decisions made [on treatment] are so crucial and will have such an effect on quality of life, men must weigh them very carefully," she says. "And they must also remember to include their partners in the decisions because they will be affected by the course of action too."

One possible treatment is actually no treatment at all. Doctors call it watchful waiting and it is best suited for men with a i0-year life expectancy or less who have a low Gleason number and whose tumor has not spread beyond the prostate. The idea is that in these men the cancer is growing so slowly, they likely won't die from it. More radical treatments such as surgery might be more dangerous than simply waiting. Marty Feins, 77, opted for watchful waiting nearly five years ago when diagnosed with prostate cancer, and he's "going great," he says. Though the Las Vegas man was deemed a good candidate for radiation treatment, he says he did a lot of research and decided his was a prudent course. His PSA level is elevated but is not rising rapidly. "Right now I'm holding steady," he says. "In fact, if I hadn't had a biopsy, I wouldn't even know I have [cancer]."

Las Vegas resident Marty Feins, 77, shown here with his wife, Evelyn, has taken a "watchful waiting" approach to his prostate cancer. Because tests show his disease to be growing very slowly, and treatments such as surgery or radiation might be dangerous at his age, Feins has decided against treatment now.

Californian Jerry Coleman, 61, diagnosed three years ago, opted for a surgical treatment called radical prostatectomy (RP), in which the prostate is completely removed. If per, formed when cancer is confined to the gland, RP is tantamount to a cure since in theory it removes all the cancer. Coleman says he chose RP because he was unsure of the track record of other treatments. "I felt comfortable that this was the appropriate attack considering my health, age, and the stage of my disease," he says.

Besides being a serious operation that requires weeks of recuperation, RP can have lingering side effects, including impotence and incontinence. Until the early 1990s, virtually all RP patients were saddled with these effects. But "nerve sparing" techniques developed at Johns Hopkins University have preserved urinary and erectile functions in increasing numbers of RP patients. The CaverMap, a device cleared by FDA earlier this year, aids surgeons in locating nerve bundles to help avoid severing nerves related to continence and erections when removing the prostate.

Radiation is a treatment option that may be less traumatic than RP and appears to have similar results when used in early-stage patients. Radiation also produces side effects, including impotence, in about half of patients. It can be applied through an external beam that directs the dose to the prostate from outside the body. FDA also has cleared low-dose radioactive "seeds," each about the size of a grain of rice, that are implanted within the prostate to kill cancer cells locally. Called brachytherapy, the seeding technique is sometimes combined with external-beam radiation for a "one-two punch." Studies done at the Georgia Center for Prostate Cancer Research and Treatment show that 68 percent of men treated with both radiation methods applied simultaneously are cancer free 10 years after treatment. Intel Corporation chairman Andy Grove, who was last year's Time magazine "Man of the Year," underwent the combined radiation therapy three years ago. According to company spokesman Howard High Grove, 61, is "in excellent condition" now.

Some prostate cancer patients opt to be treated by brachytherapy, in which radioactive "seeds" are implanted within the prostate to kill cancer cells. The seeds, about the size of a grain of rice, can be implanted through long, hollow needles (top photo) or by a Mick applicator (bottom photo), in which the seeds are loaded into a cartridge and "fired" into place in the prostate. (Photos courtesy of Indigo Medical Inc.)

Cryotherapy, in which prostate tumors are killed by freezing, shows encouraging early results. But some medical professionals consider it experimental with not enough long-term data yet to determine its effectiveness.

Hormonal therapy is often used in all phases of prostate cancer treatment to help block production or action of the make hormones that have been shown to fuel prostate cancer. Among widely used approved hormone blockers, often used in combination, are Lupron (leuprolide acetate), Casodex (bicalutamide), Eulexin (flutamide), Nilandron (nilutamide), and Zoladex (goserelin acetate implant). Because the testicles produce male hormones, some men also undergo testicle removal to cut off the hormone supply. Advanced prostate cancer patients are usually treated with any number of chemotherapeutic drugs such as Novantrone (mitoxantrone), which do not cure the disease but often do ease pain and other symptoms.

Looking Ahead

Incidences of prostate cancer have dipped slightly in the last five years, says the American Cancer Society. But as FDA's Fourcroy says, there's no "magic bullet" right now that will significantly reduce prostate cancer cases or deaths. As for the future, some strong possibilities exist.

At press time, 39 drugs and vaccines for treating prostate cancer were in clinical trials. Proposed drugs that may choke off the blood supply to prostate tumors, along with vaccines that rev up the immune system to attack prostate tumors, appear possible.

Treatments based on the hormone IGF-1, which can be a marker for increased prostate cancer risk, are feasible, researchers from McGill and Harvard Universities report.
Studies examining the relationship between diet and prostate cancer have identified a high-fat diet as a risk factor for the disease. Other diet research has shown a possible inhibitory effect for prostate cancer when foods such as soy products and cooked tomatoes are added to the diet.

A study sponsored in part by the National Cancer Institute showed that vitamin E may reduce prostate cancer risk by 30 percent, but NCI stopped short of recommending supplements.

NCI is studying 18,000 men over seven years to determine if the drug Proscar (finasteride) can prevent prostate cancer.
Meanwhile, patients are benefiting from prostate cancer's increasing visibility. "It's finally coming out of the closet," says Howard Waage, 51, a California prostate cancer patient. "It's crucial for us men to be on top of our health, and that's easier to do now than ever."


By John Henkel

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